Download Osler-Weber-Rendu Syndrome — Dental Implications

Clinical
Practice
Osler-Weber-Rendu Syndrome —
Dental Implications
Contact Author
Paulo Sérgio da Silva Santos, DDS, MD; Karin Sá Fernandes, DDS;
Marina Helena Magalhães, DDS, PhD
Dr. Fernandes
Email:
[email protected]
ABSTRACT
Osler-Weber-Rendu syndrome (OWRS) is a rare hereditary, autosomal dominant disease
characterized by a local angiodysplasia. Its clinical characteristics are vascular hamarto­
­mas of the skin and oral mucosa, arteriovenous malformations in the lungs, liver, kidney
and brain, and episodes of epistaxis. The oral lesions, which become apparent through
hemorrhagic telangiectasia, may be the first sign of the disease. This is a case report of
a 74-year-old woman whose diagnosis of OWRS was established by her dentist based
on the presence of telangiectasia in the skin and oral mucosa, reports of frequent nosebleeds of unknown etiology and a family history of telangiectasia. Amputation of a
lower limb and comorbidities, such as cardiopathy, nephropathy and rheumatic disorders, completed the profile. OWRS causes major vascular changes that can be diagnosed
initially by a dentist. In this article, we describe the skills and knowledge that dentists
need to monitor patients with OWRS properly.
For citation purposes, the electronic version is the definitive version of this article: www.cda-adc.ca/jcda/vol-75/issue-7/527.html
H
ereditary hemorrhagic telangiectasia, or
Osler-Weber-Rendu syndrome (OWRS),
was first described by Sutton in 1864
and Babington in 1865 as a hereditary epistaxis disease.1,2 In 1896, Rendu described
the disease as a pseudo hemophilia related to
hereditary epistaxis. In 1901, Osler described
the clinical symptoms of the syndrome and
emphasized its hereditary occurrence. Weber
(1907) recognized OWRS as a clinical entity
distinct from hereditary hemophilia, and
Hanes (1909) named the syndrome hereditary
hemorrhagic telangiectasia.
OWRS is an uncommon autosomal dominant disorder characterized by an angiodysplasia in the presence of telangiectasias of
the skin and oral mucosa and arteriovenous
malformations in the brain, lung, liver and
gastrointestinal tract. 3 Its incidence is 1 in
5,000–10,000 in the general population.4
Bleeding episodes may occur due to capillary fragility rather than disturbances in
coagulation.1,5
OWRS manifests itself in 2 forms: hereditary hemorrhagic telangiectasia type 1 (HHT1)
where there is mutation of the endoglin gene
on chromosome 9 with pulmonary involvement; and type 2 (HHT2) with a mutation
in the activin receptor-like kinase-1 (ALK-1)
gene. HHT2 is the milder form and its onset
is later. The proteins produced by the involved
genes may play an important role in the integrity of the vessel wall.6
The clinical characteristics of OWRS are
epistaxis, telangiectasias of the skin and oral
mucosa, visceral lesions (lungs, gastrointes-
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527
––– Fernandes –––
During the extraoral and intraoral
clinical examination, telangiectasias were
found on the skin, especially on the face
(Fig. 1) and upper limbs, and were highly
visible on the oral mucosa in the regions
of the tongue (Fig. 2), hard palate and
in the vermilion of the lip. Also present
were periodontal disease and caries.
Panoramic and periapical radiographs
were taken to develop a dental treatment
plan.
Figure 2: Telangiectasias on the
Figure 1: Telangiectasias on the face.
The patient’s signs and symptoms
tongue.
pointed toward a working diagnosis of
hereditary hemorrhagic telangiectasia
or OWRS. The patient was referred to an
Table 1 Results of blood tests
internal medicine specialist who conTest
Patient’s results
Reference value
firmed our diagnosis and began medical
INR
1
0.7–1.2
monitoring for possible systemic changes
resulting from the syndrome. Before
aPTT (s)
33 s
30–45 s
dental treatment, antibiotic prophylaxis
PT (s)
13 s
11–14.6 s
(500 mg amoxicillin) was administered
BT (min)
2.17
1–4
every 8 hours, starting 12 hours before
Platelet count (no./mm3)
280,000
165,000–397,000
the procedure and continuing for 7 days
3
after, to avoid the risk of cerebral abErythrocyte count (cells/mm )
3.97
4.3–5.9
scesses or pulmonary infections due to
Hemoglobin (g/dL)
10.9
12–16
the arteriovenous malformations found
aPTT = partial thromboplastin time, BT = bleeding time, INR = international normalized ratio,
in OWRS patients.9 Other special measPT = prothrombin time.
ures taken during treatment were use of a
vertical dental chair position to reduce
tinal tract, liver and brain) and family history.7,8 The the risk of lung and nasal bleeding, measurement of
differential diagnosis of OWRS includes benign liver blood pressure before and after the procedure, request for
disease, benign hereditary telangiectasia, CREST (cal- an up-to-date laboratory evaluation and assessment of
cinosis, Raynaud phenomenon, esophageal dysmo- her clinical condition at the time of treatment, because of
tility, sclerodactyly and telangiectasia) syndrome and the potential for renal failure and liver disease.
ataxia-telangiectasia.8
Dentists can play an important role in the diagnosis Discussion
A final diagnosis of OWRS is based on clinical criof OWRS, as its first signs often appear in the oral mu10
cosa. Moreover, the management of a patient with OWRS teria, usually the Curaçao criteria: telangiectasia on
must be suited to his or her systemic profile to ensure safe the face, hands and oral cavity; recurrent epistaxis; arteriovenous malformations with visceral invol­vement;
and efficient dental treatment.
and family history. Diagnosis is confirmed in the presence of at least 3 of these manifestations.11 In our case,
Case Report
the clinical signs of telangiectasias of the skin, espeA 74-year-old woman was referred to the special
cially in the face, upper limbs and on the oral mucosa,
care dentistry centre of our dental school for treatcombined with reported nosebleeds and a family history
ment. The patient’s medical history included congestive of telangiectasia and epistaxis were important factors
heart failure, chronic renal failure, hypertension, hypo- leading us to suspect OWRS.
thyroidism and rheumatism. Her right lower limb had
Mucocutaneous telangiectasias occur in about 90%
been surgically amputated because of vascular disorders. of cases of OWRS. 8,12 Histologically, they appear as a
She reported frequent nosebleeds and a family history of superficial collection of dilated blood vessels with a
telangiectasias and epistaxis.
layer of endothelial cells in the lamina propria. Electron
Laboratory tests showed significant changes in her red microscope studies show a lack of perivascular elastic
blood cell count—hypochromic anemia with anisocytosis fibres and smooth muscle.1
and a high level of liver enzymes, with no changes in coOnce the diagnosis is established, complementary
imaging tests, such as computed tomography ultrasound
agulation (Table 1).
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––– Osler-Weber-Rendu Syndrome –––
and magnetic resonance imaging, are important to detect
whether there is any involvement of organs, such as lungs,
liver, kidneys and the brain.10 Pulmonary arteriovenous
malformations occur in more than a third of patients
with the disease and can cause various complications,
such as hypoxia, pulmonary hemorrhage and cerebral
embolism.9 Dental professionals must be aware of these
complications, keep the dental chair in a vertical position
during dental treatment and be prepared to administer
oxygen.
Vascular lesions in the brain predispose patients to
cerebral abscesses,9 a situation that requires special care
during invasive dental procedures, such as antibiotic prophylaxis, especially in infected areas. An OWRS patient’s
risk of developing a brain abscess ranges from 5% to
9%. Few cases of cerebral abscess due to bacteremia of
odontogenic origin have been described so far. Most organisms isolated from brain abscess aspirates have been
microaerophilic and anaerobic bacteria commonly and
often specifically isolated in periodontal infections.13
Rivero-Garvia14 reported the case of a 41-year-old
patient with OWRS who had teeth extracted without
antibiotic prophylaxis and, after a few days, developed
a brain abscess. This finding confirms the importance of careful dental care in this group of patients.
Arteriovenous fistulae in the lungs and vascular malformations are important in the pathogenesis of cerebral
abscess. A peripheral septic microembolism can reach the
brain and cause a brain abscess. Approximately 10% of
patients with arteriovenous fistulae in the lungs develop
cerebral abscess.15,16
There is no evidence in the scientific literature of the
need to use antibiotic prophylaxis in invasive dental procedures that may cause bacteremia in patients with arteriovenous malformations, who have a higher likelihood
of developing cerebral abscesses. 2 However, the rarity of
the disease and lack of prospective studies addressing the
risk of brain abscesses through oral manipulation makes
the use of antibiotic prophylaxis empirical in this case.
Although for normal patients there is little risk of
exacerbation of anemia due to dental treatment, patients with OWRS with severe anemia (hemoglobin level
<10 mg/dL) should avoid certain routine procedures, as
invasive procedures can exacerbate anemia, depending
on the amount of blood that is lost.17,18
The medical treatment of OWRS is only palliative and
depends on the severity and stage of disease. Symptoms
of OWRS increase with age. Some measures, including
iron supplements, blood transfusions and laser therapy,
have met with varying degrees of success; sclerosing techniques have been used to control epistaxis. In patients
with recurrent episodes of epistaxis, surgery of the nasal
septum may be indicated.12
A study in Italy19 reported excellent hemostatic results using Nd-Yag laser treatment in 8 patients with
OWRS for the control of epistaxis and oral bleeding. This
treatment was well accepted by patients and costs were
low. However, researchers are divided on the efficiency
of the use of lasers with OWRS patients, and there is no
specific protocol for their use.
The prognosis associated with OWRS is good, but
the morbidity is significant.20 Moreover, a mortality rate
of 1%–2% is reported due to complications related to
epistaxis, and it rises to 10% in patients with cerebral
abscess.6
OWRS causes major vascular changes that may be
initially diagnosed by the dentist. Skill and knowledge
of the disease are required for proper dental monitoring
of patients with OWRS. a
THE AUTHORS
Dr. Silva Santos is a post-graduate student in the department
of oral pathology, School of Dentistry, University of São Paulo,
São Paulo, Brazil.
Dr. Fernandes is a post-graduate student in the department
of oral pathology, School of Dentistry, University of São Paulo,
São Paulo, Brazil.
Dr. Magalhães is professor and chair of the department of
oral pathology, School of Dentistry, University of São Paulo,
São Paulo, Brazil.
Correspondence to: Dr. Karin Sá Fernandes, Av. Prof. Lineu Prestes,
2227, São Paulo SP, Brazil 05508-000.
The authors have no declared financial interests.
This article has been peer reviewed.
References
1. Bartolucci EG, Swan RH, Hurt WC. Oral manifestations of hereditary
hemorrhagic telangiectasia (Osler-Weber-Rendu disease). Review and case
reports. J Periodontol. 1982;53(3):163-7.
2. te Veldhuis EC, te Veldhuis AH, van Dijk FS, Kwee ML, van Hagen
JM, Baart JA, et al. Rendu-Osler-Weber disease: update of medical and
dental considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.
2008;105(2):e38-41.
3. Letteboer TG, Zewald RA, Kamping EJ, de Haas G, Mager JJ, Snijder RJ,
et al. Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in
Dutch patients. Hum Genet. 2005;116(1-2):8-16. Epub 2004 Oct 23.
4. Begbie ME, Wallace GM, Shovlin CL. Hereditary haemorrhagic
telangiectasia (Osler-Weber-Rendu syndrome): a view from the 21st century.
Postgrad Med J. 2003;79(927):18-24.
5. Burket LW, Alderman MM, Beideman RW, Brightman VJ, Greenberg
MS, Hamner JE, et al. Hemorrhage and hemorrhagic lesions. In: Lynch MA,
editor. Burket’s oral medicine. 7th ed. Philadelphia: JB Lippincott; 1977.
p. 100-14.
6. Neville BW, Damm DD, Allen CM, Bouquet JE. Dermatologic diseases.
In: Oral and maxillofacial pathology. 2th ed. Philadelphia: Saunders; 2004.
p. 627-9.
7. Dakeishi M, Shioya T, Wada Y, Shindo T, Otaka K, Manabe M, et al.
Genetic epidemiolology of hereditary hemorrhagic telangiectasia in a local
community in the northern part of Japan. Hum Mutat. 2002;19(2):140-8.
JCDA • www.cda-adc.ca/jcda • September 2009, Vol. 75, No. 7 •
529
––– Fernandes –––
8. Sadick H, Sadick M, Götte K, Naim R, Riedel F, Bran G, et al. Hereditary
hemorrhagic telangiectasia: an update on clinical manifestations and diagnostic measures. Wien Klin Wochenschr. 2006;118(3-4):72-80.
9. Tabakow P, Jarmundowicz W, Czapiga B, Czapiga E. Brain abscess as the
first clinical manifestation of multiple pulmonary arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia (Rendu-OslerWeber disease). Folia Neuropathol. 2005;43(1):41-4.
10. Daina E, D’Ovidio F, Sabbà C. Introduction: hereditary hemorrhagic
telangiectasia as a rare disease. Curr Pharm Des. 2006;12(10):1171-2.
11. Fuchizaki U, Miyamori H, Kitagawa S, Kaneko S, Kobayashi K. Hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease). Lancet.
2003;362(9394):1490-4.
12. Folz BJ, Lippert BM, Wollstein AC, Tennie J, Happle R, Werner JA.
Mucocutaneous telangiectases of the head and neck in individuals with
hereditary hemorrhagic telangiectasia — analysis of distribution and symptoms. Eur J Dermatol. 2004;14(6):407-11.
13. Sell B, Evans J, Horn D. Brain abscess and hereditary hemorrhagic
telangiectasia. South Med J. 2008;101(6):618-25.
15. Shovlin C, Bamford K, Wray D. Post-NICE 2008: antibiotic prophylaxis
prior to dental procedures for patients with pulmonary arteriovenous malformations (PAVMs) and hereditary haemorrhagic telangiectasia. Br Dent J.
2008;205(10):531-3.
16. Shovlin CL, Jackson JE, Bamford KB, Jenkins IH, Benjamin AR, Ramadan
H, et al. Primary determinants of ischemic stroke/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary
haemorrhagic telangiectasia. Thorax. 2008;63(3):259-66. Epub 2007 Nov 2.
17. Derossi SS, Raghavendra S. Anemia. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod. 2003;95(2):131-41.
18. Glick M. Medical considerations for dental practice: an interactive CDROM. Hanover Park, Ill: Quintessence; 2005.
19. Galletta A, Amato G. [Hereditary hemorrhagic telangiectasia (OslerRendu-Weber disease) management of epistaxis and oral hemorrhage by
Nd-Yag laser]. Minerva Stomatol. 1998;47(6):283-6. [Italian]
20. McDonald MJ, Brophy BP, Kneebone C. Rendu-Osler-Weber syndrome: a current perspective on cerebral manifestations. J Clin Neurosci.
1998;5(3):345-50.
14. Rivero-Garvia M, Boto GR, Perez-Zamarron A, Alonso-Lera P, Zimman H,
Saldana CJ. [Cerebral abscess associated to Rendu-Osler-Weber disease]. Rev
Neurol. 2006;43(5):311-2. [Spanish]
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